In a new study led by atmospheric scientist Giuseppe Torri at the University of Hawai’i (UH) at M?noa School of Ocean and Earth Science and Technology (SOEST), researchers revealed details of the connection between a larger atmospheric phenomenon, termed the Madden-Julian Oscillation (MJO), and the daily patterns of rainfall in the Maritime Continent.

The MJO circles the globe around the tropics and can affect weather on weekly to monthly time scales, alternately bringing cloudy, rain periods and sunny, drier periods.

Torri and co-authors found that the impact of the MJO on the daily rainfall patterns of Sumatra was quite significant. When the MJO was active near the Maritime Continent, there was more water vapor — and therefore greater potential for significant rain events — and more variations in water vapor throughout the day as compared to the suppressed phase. Also, clouds and rain seemed to move offshore at night faster during the active phase of the MJO.

The team relied on data from a network of GPS stations that were installed on Sumatra and on the neighboring islands by a team of scientists interested in monitoring tectonic activity along the western coast of Sumatra. As it turns out, the GPS signal is distorted by the amount of water vapor in the atmosphere. This distortion is bad news for people interested in location information — which is what the GPS technology was invented for. However, scientists, including UH M?noa atmospheric sciences professor Steven Businger, realized that the distortion can tell us something about the state of the atmosphere and pioneered its use as a source of data.

With the extensive coverage of the GPS stations on the island of Sumatra, the team had a dataset that provided a highly detailed picture of the daily atmospheric changes.

“Given the existing scientific literature, we had a sense that the MJO had an impact on the local convection in the Maritime Continent,” said Torri. “One thing that was surprising to me was just how well we could see the convection propagate offshore in the late evening. This is thanks to the density of stations of the GPS network we considered.”

The MJO is arguably one of the most important phenomena on the planet, and can influence the weather and the climate of regions that are even thousands of miles away from the Maritime Continent. A better understanding of the MJO, and a good way to simulate it are key to better understanding our current and future climate.

While the current study furthers understanding of the impacts of the MJO on clouds and rain over Sumatra, Torri will team up with SOEST atmospheric scientist Alison Nugent to investigate the causes of these impacts and the mechanisms that control the offshore propagation of rainfall.

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In the study, published September 20, 2019 in PLOS One, the team demonstrated how use of a single drug — in this case nilotinib — specifically targets cancer cells that have an abnormal activation of a cell communication system, called the Hedgehog pathway, via two different mechanisms, making it more effective and less toxic than combining drugs.

“We discovered a previously unknown activity of nilotinib that may be leveraged to treat a large fraction of cases of medulloblastoma, a type of childhood brain cancer,” said senior author Ruben Abagyan, PhD, professor in the Skaggs School of Pharmacy. “While more research is needed, this pharmaceutical could potentially be used for several cancer types with an overactive cell-signaling pathway.”

Several types of basal cell carcinoma, myeloid leukemia, rhabdomyosarcoma, pancreatic adenocarcinoma, glioblastoma and one third of medulloblastoma cases have an impairment in the Hedgehog signaling pathway — a key cellular system that regulates embryonic development and adult tissue regeneration. As a result of this impairment, the cancer cells overproduce a cell-surface receptor called Smoothened. Malignancies with this abnormality account for a quarter of all cancer deaths, said Abagyan.

“Only a fraction of patients with this subtype of medulloblastoma respond well to current therapies that only target Smoothened,” said Abagyan. “Knowing that dysregulation of the Hedgehog pathway is important to the maintenance of cancer stem cells, and that it plays a critical role in several cancers, we wanted to find a single drug that inhibits this pathway in addition to several other essential anti-cancer activities.”

In the study, Abagyan and team discovered that mice bearing human medulloblastoma tumors saw tumor growth reduced and no drug resistance occurring. Nilotinib simultaneously inhibits Smoothened and several protein kinases critical for tumor growth.

Nilotinib is already a U.S. Food and Drug Administration approved therapy for chronic myeloid leukemia with a safety profile, making it a good therapeutic candidate alone or in combination with surgery, radiation therapy and chemotherapy, wrote the authors.

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In the study, researchers delivered the Penn-developed vaccine to 64 mice and then exposed them to genital herpes. After 28 days, 63 of the mice were found to have sterilizing immunity, meaning there was no trace of herpes infection or disease after the exposure. The one remaining mouse developed dormant infection without any prior genital disease. Similarly, 10 guinea pigs, which have responses to herpes infections that more closely resemble that of humans, were also given the vaccine and exposed to the virus. No animal developed genital lesions and only two showed any evidence that they became infected, but the infection was not in a form that animals could transmit the virus.

“We’re extremely encouraged by the substantial immunizing effect our vaccine had in these animal models,” said the study’s principal investigator Harvey Friedman, MD, a professor of Infectious Diseases. “Based on these results, it is our hope that this vaccine could be translated into human studies to test both the safety and efficacy of our approach.”

Building on the approaches of many cutting-edge cancer and immunotherapy researchers, the Penn team filled their vaccine with specific messenger RNA (mRNA), which can create proteins necessary for a strong immune response. This vaccine stimulates three types of antibodies: one that blocks the herpes virus from entering cells, and two others that ensure the virus doesn’t “turn off” innate immune system protective functions. This approach differs from other herpes vaccines, which often only rely on blocking virus’s entry as the mode to attack the virus.

This vaccine was developed with funding from NIH and as part of a collaboration between Penn Medicine and BioNTech, entered into in October 2018, to research and develop mRNA vaccines for various infectious diseases.

Genital herpes, also called Herpes simplex virus type 2 or HSV-2, is the most common sexually-transmitted disease. Approximately 14 percent of Americans ages 14 to 59, and 11 percent of people in the same age range across the world, are infected. HSV-2 may lead to painful sores, which can spread to other areas of the body. The virus increases one’s risk of contracting HIV, and infected pregnant women may pass herpes onto their fetus, or more commonly, to their baby during delivery.

“Along with physical symptoms, HSV-2 takes an emotional toll,” said Friedman. “People worry over transmission of the disease, and it can certainly have a negative effect on intimate relationships.”

Since herpes is so widespread but also often undetected, as it is only visible during an outbreak, researchers say a successful vaccine would be invaluable to many adults across the world.

This work was funded by the National Institutes of Health (AI045008) and BioNTech SE.

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The study examined six sugar maple stands from Virginia to Québec, Canada, over a six-year period. The sugar maple stands are located in: Divide Ridge in southwest Virginia; Southernmost Maple in central Virginia; Indiana Dunes National Lakeshore in Indiana; Harvard Forest in Massachusetts; Dartmouth Organic Farm in Hanover, New Hampshire; and Chicoutimi in Québec, Canada.

Maple syrup production is impacted by two climate sensitive factors: sugar content, which is determined by the previous year’s carbohydrate stores and sap flow, which depends on the freeze/thaw cycle. As a sugar maple tree thaws, the frozen sap begins to move through the tree.

The research team sought to test how monthly and season-long average temperatures during the tapping season, and temperature and precipitation from the preceding year, affect sap flow.

Each day of the tapping season (from January to May) across the study regions, researchers obtained sap samples from 15 to 25 mature sugar maple trees. They measured the volume and weight of the sap and conducted an analysis of the sap’s sugar content. Daily temperature readings were also taken. With this data, the team could then look at the annual variability of the sap flow, to see how the data varied from tree to tree and from year to year.

Based on historical climate data, the researchers examined how past changes in minimum and maximum temperatures affected sap flow at each of the sites. They created a model that predicted the timing for optimal sap flow based on historical temperature data pertaining to the freeze-thaw days, actual sap collection from their fieldwork, and monthly climate. To calculate projections on how climate change will affect maple syrup production, the team used climate models based on the RCP 8.5 carbon emissions scenario, which follows current emissions trends.

The study found that most sap collection seasons were 45 days or fewer and that the middle of the sugar maple tapping season tended to fall in March or later for three-quarters of the sites.

According to modeling projections, by the end of the century, the team found that tapping season is projected to be, on average, one month earlier. In addition, it is likely that by 2100, Virginia and Indiana will barely be able to produce any sap while production in Québec will be considerably enhanced. Of the states in the study, New Hampshire and Vermont (not one of the sample sites but for which climate data was analyzed) are likely to be the least affected but will still experience decreases in syrup production. By the end of the century, most of the areas containing sugar maples in the U.S. are projected to see decreases in maple syrup production while areas in northern Ontario and Québec may see moderate to large increases in production. In addition, the concentration of sap sugar is likely to become lower and more variable (28-36% lower across the modeled sites).

“As the climate gets warmer, the sugar maple tapping season will shrink and will get closer to a December date. Maple syrup producers may want to consider adapting their technologies and collection logistics in advance, so that they are prepared for how climate change is going to affect production,” said co-author David Lutz, a research assistant professor of environmental studies at Dartmouth.

In the U.S. alone, maple syrup production was valued at $141 million in 2017 according to the U.S. Department of Agriculture. As for world share, the Federation of Québec Maple Syrup Producers reported in 2017 that Canada is home to 80 percent of world maple syrup production of which 72 percent is produced in Québec, and 20 percent is produced in the U.S.

The researchers call for additional studies on climate change and maple syrup production, which can help maple syrup producers, forest managers and policymakers prepare for changes that are already impacting a multimillion-dollar industry.

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If these light structures are tightly focused by a lens, like a magnifying glass used as burning glass, highly intense three-dimensional light landscapes will be shaped, facilitating a significantly enhanced resolution in named applications. These kinds of light landscapes has paved the way to pioneering applications as Nobel prize awarded STED microscopy.

However, these nano-fields itself could not be measured yet, since components are formed by tight focusing which are invisible for typical measurement techniques. Up to now, this lack of appropriate metrological methods has impeded the breakthrough of nano-structured light landscapes as a tool for material machining, optical tweezers, or high-resolution imaging.

A team around physicist Prof. Dr. Cornelia Denz of the Institute of Applied Physics and chemist Prof. Dr. Bart Jan Ravoo of the Center for Soft Nanoscience at the University of Münster (Germany) successfully developed a nano-tomographic technique which is able to detect the typically invisible properties of nano-structured fields in the focus of a lens — without requiring any complex analysis algorithms or data post-processing. For this purpose, the team combined their knowledge in the field of nano-optics and organic chemistry to realize an approach based on a monolayer of organic molecules. This monolayer is placed in the focused light field and replies to this illumination by fluorescence, embedding all information about the invisible properties.

By the detection of this reply the distinct identification of the nano-field by a single, fast and straightforward camera image is enabled. “This approach finally opens the till now unexploited potential of these nano-structured light landscapes for many more applications,” says Cornelia Denz, who is heading the study. The study has been published in the journal Nature Communications.

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Researchers at the U.S. Department of Energy’s (DOE) Princeton Plasma Physics Laboratory (PPPL) have developed new insights into the physics governing the balance of pressure in the scrape-off layer. This balance must ensure that the pressure of the plasma throughout the tokamak is high enough to produce a largely self-heating fusion reaction. The balance must also limit the potentially damaging impact of heat and plasma particles that strike the divertor and other plasma-facing components of the tokamak.

“Previous simple assumptions about the balance of pressure in the scrape-off layer are incomplete,” said PPPL physicist Michael Churchill, lead author of a Nuclear Fusion paper that describes the new findings. “The codes that simulate the scrape-off layer have often thrown away important aspects of the physics, and the field is starting to recognize this.”

Fusion, the power that drives the sun and stars, is the fusing of light elements in the form of plasma — the hot, charged state of matter composed of free electrons and atomic nuclei — that generates massive amounts of energy. Scientists are seeking to replicate fusion on Earth for a virtually inexhaustible supply of power to generate electricity.

Key factors

Churchill and PPPL colleagues determined the key factors behind the pressure balance by running the state-of-the-art XGCa computer code on the Cori and Edison supercomputers at the National Energy Research Scientific Computing Center (NERSC), a DOE Office of Science User Facility. The code treats plasma at a detailed kinetic — or particle motion — level rather than as a fluid.

Among key features found was the impact of the bulk drift of ions, an impact that previous codes have largely ignored. Such drifts “can play an integral role” the authors wrote, and “are very important to take into account.”

Also seen to be important in the momentum or pressure balance were the kinetic particle effects due to ions having different temperatures depending on their direction. Since the temperature of ions is hard to measure in the scrape-off layer, the paper says, “increased diagnostic efforts should be made to accurately measure the ion temperature and flows and thus enable a better understanding of the role of ions in the SOL.”

The new findings could improve understanding of the scrape-off layer pressure at the divertor, Churchill said, and could lead to accurate forecasts for the international ITER experiment under construction in France and other next-generation tokamaks.

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“There is no FDA-approved or marketed technology for long-acting prevention of HIV, and we are the first to use this delivery method with multiple antiretroviral drugs,” said Rahima Benhabbour, PhD, MSc, first author of the study and assistant professor in the UNC_NCSU Joint Department of Biomedical Engineering. “To have an HIV prevention treatment that consists of an injection once or twice a year would make an incredible impact for patients.” She added, “This technology is not only promising for HIV, but for any kind of condition that requires a daily intake of medication. We’re talking about a safe, removable, long-lasting injection that takes away the burden of adhering to a daily medication regimen.”

Antiretroviral drugs are used in both prevention and treatment of HIV, and multiple types are used in combination to counteract resistance to any one antiretroviral drug. These drugs need to be taken consistently every day. There are many obstacles that stand in the way of adherence to these medication regimens. Benhabbour says this especially applies to otherwise healthy people trying to prevent infection.

“In sub-Saharan Africa where prevalence of HIV is highest, accessibility to these medications can be difficult, and there is much stigma associated with the virus,” Benhabbour said. “It is a very big deal for someone who doesn’t have HIV to go out of their way to not only access the drugs, but then associate themselves with HIV by taking a pill every day.”

There’s also the factor of human error. Anyone who strives to take a daily multivitamin can understand that some days the pill gets skipped, or gets taken at a different time of day. But such small deviations can make antiretroviral drugs less effective.

“Because one of the biggest difficulties associated with HIV prevention is lack of adherence to drug treatment, we wanted to create a drug delivery system that essentially solved this problem,” said senior author J. Victor Garcia, PhD, professor of medicine at UNC School of Medicine, director of the International Center for the Advancement of Translational Science and member of the UNC Center for AIDS Research.

The injectable implant is comprised of three elements — an organic solvent, a polymer, and the drug or drugs that need to be delivered. The formulation results in a honey-like liquid that turns into a solid when injected under the skin. This phase inversion happens when the solvent diffuses into the body leaving behind the polymer and medication(s) — the combination of which determines over what time period the medication(s) will be released into the blood system.

In this study six antiretroviral drugs were tested, and all kept their physical and chemical properties within the formulation and upon release. All six were also released from the implant at effective levels for a sustained amount of time ranging from one month to a year.

The injectable drug implant created by UNC’s research team is the first to address several drawbacks to the current method of long-acting drug delivery for HIV — namely the ability to remove it and quickly eliminate the presence of residual drug(s) in the system.

“If a patient needs to withdraw from the treatment because they’ve had a bad reaction to the drug(s), or maybe a woman has become pregnant, our implant can be easily surgically removed,” said Martina Kovarova, PhD, contributing author to the study and associate professor of medicine at UNC SOM.

This is the first ever injectable implant for HIV that can be removed as early as one week, or as late as months after the injection, and have drug levels virtually eliminated from the system within one week. If the implant does not need to be removed, it biodegrades into lactic and glycolic acids, which are already found in the body and are easily absorbed.

Researchers plan to continue developing and improving this multi-drug delivery system, observing its effects in relevant in vivo models and eventually humans.

In their study published today in Science, researchers from Australia, the United States, Canada and Finland showed that humans shaped the processes underlying how species co-existed for the last several thousand years. Smaller, surviving animals such as deer changed their ecological interactions, the researchers found, causing ecological upheaval across the continent.

The researchers’ work has implications for conservation of today’s remaining large animals, now threatened by another human-led mass extinction.

The study’s primary author is Anikó Tóth at Macquarie University in Sydney, Australia. Tóth collaborated with Villaseñor and several other researchers at the Smithsonian’s Evolution of Terrestrial Ecosystems Program, as well as researchers at other institutions.

Tóth and the co-authors focused on how large mammals were distributed across the continent in the Pleistocene and Holocene geological epochs. (The Pleistocene Epoch occurred from about 2.5 million to 11,700 years ago. Starting at the end of the Pleistocene, the Holocene is the current geological epoch.) To do this, the researchers analyzed how often pairs of species were found living in the same community or in different communities.

To rule out community changes that were the result of reduced diversity or lost associations involving extinct species, the researchers analyzed only those pairs in which both species survived. Prior to the extinction, co-occurrence was more common. After extinction, segregations were more common.

Villaseñor’s research focuses on human fossil remains as a way to understand how human ancestors interacted with mammal communities for the last 3.5 million years. Her more recent research explores how modern humans have shaped today’s ecosystems.

“Rather than thinking of humans as separate from ‘natural’ environments, our research has illuminated the major impacts that humans have had on the ecosystem for many thousands of years,” Villaseñor said. “The results of this paper and others from our group illuminate the outsized impacts that human-mediated extinction has had in North America.”

By the end of the Late Pleistocene in North America, roughly 11,000 years ago, humans contributed to the extinction of large mammals, including mammoths and sabre-toothed cats. Recent work, driven by today’s crisis in biodiversity, has looked at understanding the ecological and evolutionary legacies of this event. There was ecological transformation across the continent — the mammoth steppe disappeared, vegetation and fire regimes changed and large carnivores were lost.

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